Decitabine Enhances Acute Myeloid Leukemia Cell Apoptosis through SH3BGRL Upregulation.

BACKGROUND: SH3-domain-binding glutamic acid-rich protein-like protein (SH3BGRL) is downregulated in acute myeloid leukemia (AML). Clinically, DNA demethylating drug decitabine (DAC) combined with traditional chemotherapies reveals better efficacy on AML patients than the conventional chemotherapies alone. Our previous results revealed that human SH3-domain-binding glutamic acid-rich protein-like protein (SH3BGRL) plays a tumor suppressive role in AML but whether there is a connection between DAC and SH3BGRL expression remains elusive. METHODS: Here, we tentatively treated AML cell lines U937, MV4, and HL-60 with DAC and Western Blots, RT-PCR was used to detect the expression of SH3BGRL. Cell proliferation and apoptosis were determined using Annexin V/7- AAD staining. Real-time RT-PCR and Western blot were used to determine the expression of SH3BGRL mRNA and protein. Methylation-specific PCR was used to quantify the DNA methylation in AML cell lines. RESULTS: DAC had cytotoxicity in HL-60, MV4, and U937. In U937 cell lines, treatment with DAC showed the upregulation of cleaved caspase3, PARP, and SH3BGRL. Upon treatment, up-regulation of SH3BGRL mRNA and protein was dose-dependent and this activity was partially inhibited in endogenous SH3BGRL knockdown cell lines. CONCLUSION: Thus, our results demonstrated a possibly cytotoxic role of DAC on AML cells by upregulation of SH3BGRL expression at epigenetic modulation level and the methylation status in the SH3BGRL promoter region could be a supplemental diagnostic marker to the precise administration of DAC to AML patients.

Tougu Xiaotong capsules may inhibit p38 MAPK pathway-mediated inflammation: In vivo and in vitro verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Tougu Xiaotong capsules (TXC) are an herbal compound commonly used to treat osteoarthritis (OA) in China. AIM OF THE STUDY: We attempted to verify TXC's therapeutic effects and mechanisms related to the p38 mitogen-activated protein kinase (MAPK) pathway in vivo and in vitro. MATERIALS AND METHODS: TXC's therapeutic effects were assessed by observing cartilage degeneration and inflammatory factors in a modified Hulth's model (in vivo) and a lipopolysaccharides (LPS)-exposed cellular model (in vitro). The expression of biomarkers related to p38 MAPK pathway-mediated inflammation was also investigated. RESULTS: TXC treatment reversed cartilage degeneration related biomarkers (ADAMTS 4, ADAMTS 5, Col I, Col V, MMP 3, MMP 9, and MMP 13) and inflammation factors (IL-1ß, TNF-α, and IL-6) in both the animal and cellular OA models. Expression of p-p38 MAPK was downregulated following TXC administration, and changes to microRNAs in the cellular models were recovered. These results indicated that the p38 MAPK pathway-related mechanism may involve therapeutic effects of TXC. CONCLUSIONS: This study verified TXC's efficacy to treat OA in vivo and in vitro and suggests that p38 MAPK pathway-related mechanisms may be involved in TXC's therapeutic effects.

Characterization and evolution of antibiotic resistance of Salmonella in municipal wastewater treatment plants.

The objective of this study was to investigate the evolution of antibiotic resistance phenotypes, antibiotic resistance genes (ARGs) and Class 1 integron of Salmonella in municipal wastewater treatment plants (WWTPs). A total of 221 Salmonella strains were isolated from different stages of three WWTPs. After the susceptibility testing, high frequency of resistance was observed for tetracycline (TET, 47.5% of isolates) and sulfamethoxazole (SMZ, 38.5%), followed by ampicillin (AMP, 25.3%), streptomycin (STP, 17.6%), chloramphenicol (CHL, 15.4%), and gentamicin (GEN, 11.3%). Low prevalence of resistance was detected for norfloxacin (0.45%), ciprofloxacin (0.9%), and cefotaxime (0.9%). The tetA and sul3 genes were most frequently detected among the Salmonella isolates. Statistically significant correlations among AMP, CHL, GEN, and STP resistances were observed. High detection frequencies of Class 1 integron were observed in double antibiotic-resistant and multiple-antibiotic-resistant (MAR) Salmonella, which were 94.3% and 85.7%, respectively. The proliferation of MAR Salmonella and transfer of ARGs occurred in WWTPs. Class 1 integron plays a crucial role in the evolution of MAR Salmonella during WWTPs.

Combination of inspiratory and expiratory muscle training in same respiratory cycle versus different cycles in COPD patients: a randomized trial.

BACKGROUND: Difference between combined inspiratory and expiratory muscle training in same respiratory cycle or different cycles remained unclarified. We explored the difference between both patterns of combined trainings in patients with COPD. METHODS: In this randomized, open-label, controlled trial, stable COPD subjects trained for 48 minutes daily, for 8 weeks, using a monitoring device for quality control. Ninety-two subjects were randomly and equally assigned for sham training, inspiratory muscle training(IMT), combined inspiratory and expiratory muscle training in same cycle(CTSC) or combined inspiratory and expiratory muscle training in different cycles(CTDC). Respiratory muscle strength, as the primary endpoint, was measured before and after training. Registry: ClinicalTrials.gov (identifier: NCT02326181). RESULTS: Respiratory muscle training improved maximal inspiratory pressure(PImax), while no significant difference was found in PImax among IMT, CTSC and CTDC. Maximal expiratory pressure(PEmax) in CTSC and CTDC was greater than IMT(P = 0.026, and P=0.04, respectively) and sham training (P = 0.001). IMT, CTSC, and CTDC shortened inhalation and prolonged exhalation(P < 0.01). Subjects with respiratory muscle weakness in IMT and CTDC exhibited greater increase in PImax than those without. IMT, CTSC and CTDC showed no difference in symptoms and quality of life scales among themselves(P > 0.05). CONCLUSION: Both patterns of CTSC and CTDC improved inspiratory and expiratory muscle strength, while IMT alone only raised PImax. Respiratory muscle training might change the respiratory cycles, and be more beneficial for COPD patients with inspiratory muscle weakness.

Safety and effectiveness of Traditional Chinese Medicinal herbs for diabetic foot: a systematic review and Meta-analysis.

OBJECTIVE: To evaluate the safety and effectiveness of traditional Chinese medicinal herbs (TCMHs) as an adjunctive treatment for diabetic foot (DF). METHODS: The sources used were PubMed (1966 to August 2015), the Cochrane Library (1988 to August 2015), the Excerpta Medica Database (1974 to August 2015), Wiley (1807 to August 2015), Ovid (1988 to August 2015), ClinicalTrials.gov (1993 to August 2015), the Cochrane Central Register of Controlled Trials (1966 to August 2015), China Science and Technology Journal Database (1994 to August 2015), ChiCTR (2007 to August 2015), SinoMed (1978 to August 2015), the China National Knowledge Infrastructure (1984 to August 2015), Wanfang Data Knowledge Service Platform (1998 to August 2015), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS) (1984 to August 2015). Studies were identified and selected, and the data were extracted by two independent reviewers. The Cochrane Risk of Bias tool was used to assess the quality of studies. Revman 5.2 software was used for data synthesis and analysis. RESULTS: Sixteen studies were included based on the selection criteria. Of these, seven studies had low bias risk and one had high bias risk. In the overall analysis, TCMHs resulted in a significantly higher total effective rate (OR 5.08; 95% CI 3.50 to 7.36; P < 0.000 01), cure rate (OR 2.12; 95% CI 1.63 to 2.77; P < 0.000 01), and shorter time to ulcer healing (SMD －0.64; 95% CI －0.89 to －0.40; P < 0.000 01) when compared with non-TCMHs treated DF. The analysis also revealed that significantly fewer amputations occurred in TCMHs patients (OR 0.36; 95% CI 0.20 to 0.65; P = 0.0007). Sensitivity analysis indicated that the findings of the Meta-analysis were robust to study quality, and the funnel plot of the Egger test showed no publication bias. CONCLUSION: TCMHs intervention appears to be more effective for DF, with a similar safety profile, when compared with non-TCMHs treatments, although this result requires further verification with more well-designed studies.

Neferine induces autophagy of human ovarian cancer cells via p38 MAPK/ JNK activation.

Ovarian cancer is the most lethal gynecological malignancy. Patients usually have poor prognosis because of late diagnosis, relapse, and chemoresistance. It is pressing to seek novel agent for the treatment of ovarian cancer. Neferine is a bisbenzylisoquinoline alkaloid isolated from the embryos of lotus (Nelumbo nucifera). In this study, we investigated the antitumor effect of neferine on ovarian cancer cells. We found that neferine exhibited growth-inhibitory effect on human ovarian cancer cells, whereas showing less cytotoxic to non-malignant fallopian tube epithelial cells. Furthermore, we demonstrated that neferine induced autophagy and inactivated the mTOR pathway. Finally, we found that both p38 MAPK and JNK signaling pathways were activated by neferine treatment and contributed to the induction of autophagy in ovarian cancer cells. In conclusion, our findings showed that neferine induced autophagy of human ovarian cancer cells via p38 MAPK/JNK activation. Neferine may be explored as a promising antitumoral agent in ovarian cancer.

Effects of zishentongluo in patients with early-stage diabetic nephropathy.

The purpose of this study was to assess the efficacy of zishentongluo (ZSTL) for the treatment of diabetic nephropathy (DN) and its related mechanisms. Forty-five patients with DN were randomized to receive either ZSTL (n = 25) or benazepril (n = 20), an angiotensin converting enzyme inhibitor, for 12 weeks. Conventional biochemical tests were performed to determine fasting blood glucose (FBG), glycated hemoglobin (HbA1c), serum creatinine (SCr), endogenous creatinine clearance rate (Ccr), total cholesterol (TC), and triglyceride (TG) levels. The urinary albumin excretion rate (UAER), and endothelin 1 (ET-1), and atrial natriuretic peptide (ANP) levels were determined with a radioimmunoassay, and vascular endothelial growth factor (VEGF) was detected using an enzyme-linked immunosorbent assay. The primary endpoint was change from the baseline to post-treatment in HbA1c. Secondary endpoints were change from baseline to post-treatment in FBG, TC, TG, UAER, SCr, Ccr, VI-C, ANP, ET-1, and VEGF. ZSTL was significantly more effective at improving the primary (i.e., HbA1c) and secondary (i.e., FBG, TC, TG, UAER, SCr, ANP, ET-1, and VEGF) outcomes than benazepril (p < 0.05). These findings suggest that ZSTL is superior to benazepril at improving the metabolic and renal functioning in patients with early-stage DN, in part, by modifying ANP, ET-1, and VEGF.